1. Field of Invention
The present invention relates to a method for preparing a precursor of radioactive agents, especially to a method for preparing N,N′-bis(tert-butyloxycarbonyl)-3-(tri-n-butyltin)benzylguanidine) (MSnBG), a precursor of radioactive 3-iodobenzylguanidine.
2. Description of Related Art
After being found in 1980s, 3-iodobenzylguanidine (Meta-iodo-benzyl-guanidine, MIBG) labeled with I-123 and I-131 ([123I]MIBG and [131I]MIBG) has been used as imaging agents for diagnosis of various diseases such as heart diseases and neuroblastoma. Moreover, the half-life of I-131 gives the value 80.5 days and the energy released per decay is 0.97 MeV so that it can be used for the radiation therapy of tumors. Thus [131I]MIBG is also used as an antineoplastic agent for treatment of neuroblastoma in the image-guided radiation therapy.
For a long time, radioiodine labeled MIBG([*I]MIBG) is prepared by an isotopic exchange method using an radioiodide (I-131 or I-125), as shown in FIG. 1. Beside MIBG with radioactive iodine, the product obtained by this method contains a significant amount of initial reactant-MIBG with natural iodine. The two materials are difficult to separate with each other. While being applied to antineoplastic agents, after being injected into humans, [*I]MIBG and MIBG compete with each other to bind with specific receptors. The amount of MIBG is far more larger than the [*I]MIBG so that a large amount of receptors are occupied by MIBG. Thus effective [*I]MIBG is unable to react with receptors and the effects of radiation therapy have been affected.
Although in the study of G. Vaidyanathan, D. J. Affleck, K. L. Alaton and M. R. Zalutsky, J. Label. Comp. Radiopharm., 50, 177-182 (2007), a similar precursor to be labeled is revealed. However, a method for manufacturing the precursor is disclosed by Dodd and A. P. Kozikowski, Tetrahedron Lett., 35, 977-979 (1994) and G. Vaidyanathan and M. R. Zalutsky, J. Org. Chem., 62, 4867-4869 (1997), as shown in FIG. 2. Moreover, the leaving group of the precursor (C14) to be labeled is (CH3)3Sn.